We calculated the time required for therapeutic benefit to become apparent following initiation of treatment with D-penicillamine (DP), hydroxychloroquine (HCQ), or placebo (each administered concomitantly with a nonsteroidal antiinflammatory drug) using data from a double-blind, randomized 12-month trial in 162 patients with juvenile rheumatoid arthritis. Using previously published criteria to classify the outcome, we found that 60% of the HCQ group, 46% of the DP group, and 39% of the placebo group responded favorably after 12 months of therapy. Data from examinations between the initial and final assessments were used to determine when the response first occurred. Approximately 50% of all patients who showed improvement at 12 months had already done so by 2 months. After 6 months, 96% of the DP group, 88% of the HCQ group, and 85% of the placebo group responders had met the criteria for response. The average time until response was attained was 105 days for the DP group, 129 days for the HCQ group, and 140 days for the placebo group. Our results indicate that a favorable response to these slow-acting antirheumatic drugs is unlikely if improvement has not occurred within the first 6 months of therapy.